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Studies have found that the high-dose influenza vaccine has a higher relative vaccine effectiveness (RVE) versus standard-dose vaccines in some seasons. We evaluated the effect of age on the RVE of high-dose versus standard-dose influenza vaccines among Medicare beneficiaries. A 6-season retrospective cohort study from 2012 to 2018 among Medicare beneficiaries aged ≥65 years was performed. Poisson regression was used to evaluate the effect of age on the RVE of high-dose versus standard-dose influenza vaccines in preventing influenza-related hospitalizations. The study included >19 million vaccinated beneficiaries in a community pharmacy setting. The Poisson models indicated a slightly increasing trend in RVE with age in all seasons. The high-dose vaccine was more effective than standard-dose vaccines in preventing influenza-related hospital encounters (ie, influenza-related inpatient stays and emergency department visits) in the 2012-2013 (RVE, 23.1%; 95% confidence interval [CI], 17.6%-28.3%), 2013-2014 (RVE, 15.3%; 95% CI, 7.8%-22.3%), 2014-2015 (RVE, 8.9%; 95% CI, 5.6%-12.1%), and 2016-2017 (RVE, 12.6%; 95% CI, 6.3%-18.4%) seasons and was at least as effective in all other seasons. We also found that the high-dose vaccine was consistently more effective than standard-dose vaccines across all seasons for people aged ≥85 years. Similar trends were observed for influenza-related inpatient stays. The RVE of high-dose versus standard-dose influenza vaccines increases with age.

Persons with end stage kidney disease (ESKD) on dialysis are at high risk for severe COVID-19 disease. In September 2023, 2023–2024 COVID-19 vaccination was recommended in the United States for all persons aged ≥6 months. Due to possible immune dysfunction, advanced age, and high prevalence of additional underlying conditions, including immunocompromising conditions, among individuals with ESKD, reduced vaccine effectiveness (VE) is a concern. Understanding effectiveness of 2023–2024 COVID-19 vaccine among persons with ESKD can inform COVID-19 vaccine recommendations for this population. A retrospective cohort investigation was conducted among Medicare fee-for-service beneficiaries aged ≥18 years with ESKD receiving dialysis using Medicare enrollment and claims records. Follow-up began on September 17, 2023, and continued until the earliest occurrence of claim for a COVID-19–associated outcome, other censoring event, or end of follow-up. A marginal structural Cox model was used to estimate VE (calculated as [1 – hazard ratio]*100 %), interpreted as the benefit of 2023–2024 COVID-19 vaccination compared with no 2023–2024 vaccine dose. VE was estimated by presence of additional immunocompromising conditions, age group, and time since vaccination. During September 17, 2023 – April 13, 2024, 17,749/112,250 (16 %) Medicare beneficiaries aged ≥18 years with ESKD without additional immunocompromising conditions received a 2023–2024 COVID-19 vaccine dose, with a maximum 209 days of follow-up since vaccination. During the follow-up period 6539 medically attended COVID-19 events, including 3605 COVID-19-associated hospitalizations, 789 COVID-19-associated deaths, and 896 COVID-19-associated thromboembolic events, were recorded. VE against COVID-19-associated hospitalization was 55 % (95 % confidence interval [CI]: 42 % - 65 %) at 7–59 days after vaccination and 47 % (95 % CI: 35 % – 57 %) at ≥60 days after vaccination. VE against COVID-19-associated death was 71 % (95 % CI: 46 % - 84 %) at 7–59 days after vaccination and 51 % (95 % CI: 24 % – 69 %) ≥60 days after vaccination. VE against COVID-19-associated thromboembolic events was 44 % (95 % CI, 24 %, 59 %). The 2023–2024 COVID-19 vaccines provided protection against COVID-19-associated hospitalization, death, and thromboembolic events among adults with ESKD. These data support the recommendation that adults with ESKD receive the updated COVID-19 vaccine. •End stage kidney disease (ESKD) is associated with increased risk of severe COVID-19.•Uptake of 2023–2024 COVID-19 vaccination among adults with ESKD was low.•COVID-19 vaccination was effective against severe COVID-19 among adults with ESKD.•COVD-19 vaccine effectiveness among adults with ESKD waned with more time since vaccination.

COVID-19 has been associated with an increased risk for thromboembolic events, including ischemic stroke, venous thromboembolism, and myocardial infarction. Studies have reported lower rates of COVID-19-related thromboembolic events among persons who received the COVID-19 vaccine compared with persons who did not, but rigorous estimates of vaccine effectiveness (VE) in preventing COVID-19-related thromboembolic events are lacking. This analysis estimated the incremental benefit of receipt of a bivalent mRNA COVID-19 vaccine after receiving an original monovalent COVID-19 vaccine. To estimate VE of a bivalent mRNA COVID-19 dose in preventing thromboembolic events compared with original monovalent COVID-19 vaccine doses only, two retrospective cohort studies were conducted among Medicare fee-for-service enrollees during September 4, 2022-March 4, 2023. Effectiveness of a bivalent COVID-19 vaccine dose against COVID-19-related thromboembolic events compared with that of original vaccine alone was 47% (95% CI = 45%-49%) among Medicare enrollees aged ≥65 years and 51% (95% CI = 39%-60%) among adults aged ≥18 years with end stage renal disease receiving dialysis. VE was similar among Medicare beneficiaries with immunocompromise: 46% (95% CI = 42%-49%) among adults aged ≥65 years and 45% (95% CI = 24%-60%) among those aged ≥18 years with end stage renal disease. To help prevent complications of COVID-19, including thromboembolic events, adults should stay up to date with COVID-19 vaccination.

Prostate cancer (PC) is the most common cancer diagnosed in men worldwide. Currently, castration-resistant prostate cancer (CRPC), which is resistant to androgen deprivation therapy, has a poor prognosis and is a therapeutic problem. We investigated the antitumor effects on PC of an antibody neutralizing secreted disintegrin and metalloproteinase domain-containing protein 9 (sADAM9), which is a blood-soluble form. We performed proliferation assays, wound healing assays, invasion assays, Western blot (WB), and an in vivo study in which a sADAM9 neutralizing antibody was administered intratumorally to PC-bearing mice. In invasion assays, the sADAM9 neutralizing antibody significantly inhibited invasion in all cell lines (TRAMP-C2: p = 0.00776, LNCaP: p = 0.000914, PC-3: p = 0.0327, and DU145: p = 0.0254). We examined epithelial–mesenchymal transition (EMT) markers, one of the metastatic mechanisms, in WB and showed downregulation of Slug in TRAMP-C2, LNCaP, and DU145 and upregulation of E-cadherin in TRAMP-C2 and PC-3 by sADAM9 neutralization. In mouse experiments, the sADAM9 neutralizing antibody significantly suppressed tumor growth compared to controls (1.68-fold in TRAMP-C2, 1.89-fold in LNCaP, and 2.67-fold in PC-3). These results suggested that the sADAM9 neutralizing antibody inhibits invasion, migration, and tumor growth in PC. Previous studies examined the anti-tumor effect of knockdown of total ADAM9 or sADAM9, but this study used the new technology of neutralizing antibodies for sADAM9. This may be novel because there was no animal study using a neutralizing antibody for sADAM9 to see the relationship between ADAM9 expression and prostate cancer.

Most cases of hepatocellular carcinoma (HCC) arise with the fibrotic microenvironment where hepatic stellate cells (HSCs) and carcinoma-associated fibroblasts (CAFs) are critical components in HCC progression. Therefore, CAF normalization could be a feasible therapy for HCC. Galectin-1 (Gal-1), a β-galactoside-binding lectin, is critical for HSC activation and liver fibrosis. However, few studies has evaluated the pathological role of Gal-1 in HCC stroma and its role in hepatic CAF is unclear. Here we showed that Gal-1 mainly expressed in HCC stroma, but not cancer cells. High expression of Gal-1 is correlated with CAF markers and poor prognoses of HCC patients. In co-culture systems, targeting Gal-1 in CAFs or HSCs, using small hairpin (sh)RNAs or an therapeutic inhibitor (LLS30), downregulated plasminogen activator inhibitor-2 (PAI-2) production which suppressed cancer stem-like cell properties and invasion ability of HCC in a paracrine manner. The Gal-1-targeting effect was mediated by increased a disintegrin and metalloprotease 17 (ADAM17)-dependent TNF-receptor 1 (TNFR1) shedding/cleavage which inhibited the TNF-α → JNK → c-Jun/ATF2 signaling axis of pro-inflammatory gene transcription. Silencing Gal-1 in CAFs inhibited CAF-augmented HCC progression and reprogrammed the CAF-mediated inflammatory responses in a co-injection xenograft model. Taken together, the findings uncover a crucial role of Gal-1 in CAFs that orchestrates an inflammatory CSC niche supporting HCC progression and demonstrate that targeting Gal-1 could be a potential therapy for fibrosis-related HCC.